Brain Pathology Case of the Month - April 2008

DIAGNOSIS AND DISCUSSION

Diagnoses

Primary acalvaria

Polymicrogyria

Partial destruction of brain stem and cerebellum

Discussion

Acalvaria is a rare congenital malformation characterized by an absence of calvarial bones and dura mater, in the presence of a normal skull base, facial bones, and scalp. This entity has been observed currently with a multitude of anatomic CNS findings, including hydrocephalus and holoprosencephaly, and polymicrogyria (1, 2). In the present case, by gross examination the brain stem region appeared to be sub-totally replaced by fibroadipose tissue and well-formed cerebellar tissue was not identified; however, microscopic examination revealed residual brain stem nuclei as well as focal cerebellar tissue. As such, the partial replacement of normal anatomic structures are believed to reflect a destructive process whereby native CNS parenchyma is focally replaced by connective tissue, as opposed to reflecting additional co-existing primary malformative lesions.

Acalvaria has also been observed in association with non-CNS findings including cardiac anomalies, omphalocele, hypertelorism, cleft lip and palate, renal tubular dysgenesis, and concomitantly with the amniotic band syndrome (1, 3-5). Most cases are fatal, although rare living cases have been described (6, 7).

The precise pathogenesis of acalvaria is currently unknown. One theory postulates that it reflects a post-neurulation defect with faulty migration of mesenchyme, but with normal placement of embryonic ectodermal derivatives. Consequently, there is absence of the calvarium, but an intact layer of skin covers the brain parenchyma, as is demonstrated in this case. Another theory postulates that acalvaria results from primary non-closure of the neural tube, and that this entity exists within and along a pathogenesis spectrum that includes anencephaly (1, 8, 9).

As a heterogeneous disorder, acalvaria has also been described in settings where peri-conception teratogenic exposure had not been apparent, where other birth defects were absent, and where fetal karyotyping had been normal (3). Prevention by prenatal and perinatal folic acid consumption has not been described; however, high-alpha-fetoprotein levels in conjunction with undetectable unconjugated estriol levels during the fetal period have been observed (6, 8). However, associations with parental consanguinity (6) and with ACE-inhibitor administration have been reported (9). Currently, no specific risk of recurrence has been documented in the subsequent pregnancies of women with acalvarial neonates.

This case illustrates an example of acalvaria with findings of polymicrogyria and partial destruction of cerebellar brain tissue, associated with antepartum maternal tobacco and drug use. The maternal history of drug and tobacco use is regarded as an incidental association, and thus no inference into the direct or indirect cause-effect relationship can be made.